Archive for June 11, 2012

Antibiotic choice may not explain poorer outcomes in patients with Staphylococcus aureus bacteremia and high vancomycin minimum inhibitory concentrations.

J Infect Dis. 2011 Aug 1 V.204 N.3 P.340-7.

Holmes NE, Turnidge JD, Munckhof WJ, Robinson JO, Korman TM, O’Sullivan MV, Anderson TL, Roberts SA, Gao W, Christiansen KJ, Coombs GW, Johnson PD, Howden BP.

Department of Infectious Diseases, Austin Health, Heidelberg, Australia.



There are concerns about reduced efficacy of vancomycin in patients with Staphylococcus aureus bacteremia (SAB), especially when the minimum inhibitory concentration (MIC) nears the upper limit of the susceptible range.


We examined the relationship between antibiotic treatment, 30-day mortality, and microbiologic parameters in a large Australasian cohort of patients with SAB.


We assessed 532 patients with SAB from 8 hospitals. All patients with methicillin-resistant S. aureus (MRSA) bacteremia were treated with vancomycin, and patients with methicillin-susceptible S. aureus (MSSA) bacteremia received either flucloxacillin or vancomycin. Increasing vancomycin MIC was associated with increased mortality in vancomycin-treated patients. However, even in patients with MSSA bacteremia treated with flucloxacillin, mortality was also higher if the vancomycin Etest MIC of their isolate was >1.5 μg/mL, compared with those with lower MIC isolates (26.8% vs 12.2%; P < .001). After adjustment in a multivariate model, age, hospital-onset SAB and vancomycin MIC were independently associated with mortality, but methicillin resistance and antibiotic choice were not.


We have confirmed an association between higher vancomycin MIC and increased mortality in patients with SAB, but surprisingly this relationship was not related to the antibiotic treatment received, suggesting that the use of vancomycin per se is not responsible for the poorer outcome.


June 11, 2012 at 10:13 pm

Ethical dilemmas in antibiotic treatment

Journal of Antimicrobial Chemotherapy   Jan 2012 V.67  N.1  P.12-16

Leonard Leibovici1,2,*, Mical Paul2,3 and Ovadia Ezra4

1Department of Medicine E, Beilinson Hospital, Rabin Medical Center, Petah-Tiqva, Israel

2Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

3Unit of Infectious Diseases, Beilinson Hospital, Rabin Medical Center, Petah-Tiqva, Israel

4Philosophy Department, The Lester and Sally Entin Faculty of Humanities, Tel-Aviv University, Tel-Aviv, Israel

Patients with moderate to severe infections are given less than maximum empirical antibiotic treatment in order to reduce the rise in resistance. This practice involves two ethical dilemmas: whether the danger to a present patient should be increased (even if by a small degree) to benefit future, unidentified patients; and whether this should be done without the consent of the patient, disregarding the patient’s autonomy. We argue that future patients have a right to come to no harm. Future patients being unidentified, practitioners of medicine have a duty to protect their rights and weigh them against the rights of the present patient. A decision on the collective (guidelines, decision support systems) is a convenient way to do that. Using a temporal discount rate to show that the life of present patients has pre-eminence, to some degree, over future patients does not solve the immediacy of the plight facing a present, identified patient with a very severe infection. We think there are good grounds to take into less account considerations of future resistance for such a patient, or in a formal analysis, to make the ratio of benefits to the present versus future patients dependent on the severity of disease of the present patient. None of these solve the problem of patients’ autonomy. We see no other way but to argue that the right of future patients to come to less harm outweighs the right of the present patient to share in decisions on antibiotic treatment.



June 11, 2012 at 2:14 pm

Pharmacogenetics of hepatitis C

Journal of Antimicrobial Chemotherapy   March 2012 V.67  N.3  P.523-529

Vincent Soriano*, Eva Poveda, Eugenia Vispo, Pablo Labarga, Norma Rallón and Pablo Barreiro

Infectious Diseases Department, Hospital Carlos III, Madrid, Spain

Recent discoveries have highlighted the influence of host genomics on hepatitis C virus (HCV) infection outcomes. As a result, our views on hepatitis C pathogenesis and therapeutic approaches have been transformed. The recognition of the impact of single-nucleotide polymorphisms (SNPs) of the genes interleukin 28B (IL28B), inosine triphosphatase (ITPA) and low-density lipoprotein cholesterol receptor (LDLR) may lead to refinements in the pharmacogenomic prediction of antiviral response and drug-related toxicities and favour the discovery of new therapeutic targets for hepatitis C. Although the relevance of host genetics may be less in the setting of very potent new direct-acting antivirals (DAAs), genetic markers may continue to aid decision making regarding the length of therapy. Moreover, in several populations, such as HIV/HCV-coinfected patients, current therapy with peginterferon-α/ribavirin will continue in use for most patients, and thus host factors will retain their predictive value for treatment outcomes for a while.


June 11, 2012 at 2:13 pm

Are susceptibility tests enough, or should laboratories still seek ESBLs and carbapenemases directly?

Journal of Antimicrobial Chemotherapy   July 2012 V.67  N.7  P.1569-1577

David M. Livermore1,2,*, Jenny M. Andrews3, Peter M. Hawkey4, Pak-Leung Ho5, Yoram Keness6, Yohei Doi7, David Paterson8 and Neil Woodford2

1Norwich Medical School, University of East Anglia, Norwich, UK

2Antibiotic Resistance Monitoring & Reference Laboratory, Health Protection Agency—Colindale, London, UK

3Department of Microbiology, Sandwell and West Birmingham NHS Trust, City Hospital, Birmingham, UK

4School of Immunity and Infection, The Medical School, University of Birmingham, Edgbaston, Birmingham, UK

5Department of Microbiology and Carol Yu Centre for Infection, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China

6Clinical Microbiology Laboratory, Emek Medical Center, Afula, Israel

7Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

8University of Queensland Centre for Clinical Research, Royal Brisbane and Women’s Hospital Campus, Brisbane, Australia

Recent EUCAST advice asserts that, with low breakpoints, susceptibility results for cephalosporins and carbapenems can be reported ‘as found’, even for strains with extended-spectrum β-lactamases (ESBLs) and carbapenemases. The CLSI has similar advice, but with higher ceftazidime and cefepime breakpoints than those of EUCAST. Pharmacodynamic and animal data are used to support these views, along with some analysis of clinical case series. We contend that such advice is misguided on three counts. First, whilst there are cases on record where cephalosporins and carbapenems have proved effective against infections due to low-MIC ESBL producers and low-MIC carbapenemase producers, respectively, there are similar numbers of cases where such therapy has failed. Second, routine susceptibility testing is less precise than in research analyses, meaning that ESBL and carbapenemase producers with ‘real’ MICs of 1–8 mg/L will oscillate between susceptibility categories according to who tests them and how. Third, although EUCAST continues to advocate ESBL and carbapenemase detection for epidemiological purposes, the likely consequence of not seeking these enzymes for treatment purposes is that some laboratories will not seek them at all, leading to a loss of critical infection control information. In short, it is prudent to continue to seek ESBLs and carbapenemases directly and, where they are found, generally to avoid substrate drugs as therapy.


June 11, 2012 at 2:10 pm


June 2012

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